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      Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update


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          Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts’ personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.

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          GRADE: an emerging consensus on rating quality of evidence and strength of recommendations.

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            Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008.

            Estimates of the worldwide incidence and mortality from 27 cancers in 2008 have been prepared for 182 countries as part of the GLOBOCAN series published by the International Agency for Research on Cancer. In this article, we present the results for 20 world regions, summarizing the global patterns for the eight most common cancers. Overall, an estimated 12.7 million new cancer cases and 7.6 million cancer deaths occur in 2008, with 56% of new cancer cases and 63% of the cancer deaths occurring in the less developed regions of the world. The most commonly diagnosed cancers worldwide are lung (1.61 million, 12.7% of the total), breast (1.38 million, 10.9%) and colorectal cancers (1.23 million, 9.7%). The most common causes of cancer death are lung cancer (1.38 million, 18.2% of the total), stomach cancer (738,000 deaths, 9.7%) and liver cancer (696,000 deaths, 9.2%). Cancer is neither rare anywhere in the world, nor mainly confined to high-resource countries. Striking differences in the patterns of cancer from region to region are observed. Copyright © 2010 UICC.
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              Management of hepatocellular carcinoma: An update

              Since the publication of the American Association for the Study of Liver Diseases (AASLD) practice guidelines on the management of hepatocellular carcinoma (HCC) in 2005, new information has emerged that requires that the guidelines be updated. The full version of the new guidelines is available on the AASLD Web site at http://www.aasld.org/practiceguidelines/Documents/Bookmarked%20Practice%20Guidelines/HCCUpdate2010.pdf. Here, we briefly describe only new or changed recommendations. Surveillance and Diagnosis In the previous guideline, groups were specified for which surveillance was likely to be cost-effective because the hepatocellular carcinoma (HCC) incidence was high enough. New data on defining HCC risk have emerged for hepatitis B virus,1,2 hepatitis C virus,3 and autoimmune hepatitis.4 Surveillance is deemed cost-effective if the expected HCC risk exceeds 1.5% per year in patients with hepatitis C and 0.2% per year in patients with hepatitis B. Analysis of recent studies show that alpha-fetoprotein determination lacks adequate sensitivity and specificity for effective surveillance (and for diagnosis).5,6 Thus, surveillance has to be based on ultrasound examination. The recommended screening interval is 6 months. Diagnosis of HCC should be based on imaging techniques and/or biopsy.The 2005 diagnostic algorithm has been validated and the diagnostic accuracy of a single dynamic technique showing intense arterial uptake followed by “washout” of contrast in the venous-delayed phases has been demonstrated.7-9 Contrast-enhanced US may offer false positive HCC diagnosis in patients with cholangiocarcinoma and thus, has been dropped from the diagnostic techniques. The diagnostic algorithm is shown in Fig. 1. The application of dynamic imaging criteria should be applied only to patients with cirrhosis of any etiology and to patients with chronic hepatitis B who may not have fully developed cirrhosis or have regressed cirrhosis. Interpretation of biopsies and distinction between high-grade dysplatic nodules and HCC is challenging. Expert pathology diagnosis is reinforced by staining for glypican 3, heat shock protein 70, and glutamine synthetase, because positivity for two of these three stains confirms HCC.10 Fig. 1 Diagnostic algorithm for suspected HCC. CT, computed tomography; MDCT, multidetector CT; MRI, magnetic resonance imaging; US, ultrasound. Staging and Treatment of HCC The BCLC staging system (Fig. 2)11 has come to be widely accepted in clinical practice and is also being used for many clinical trials of new drugs to treat HCC. Therefore, it has become the de facto staging system that is used. Fig. 2 The BCLC staging system for HCC. M, metastasis classification; N, node classification; PS, performance status; RFA, radiofrequency ablation; TACE, transarterial chemoembolization. The recommendations for liver transplantation have not changed. No new data have emerged that can be used to define a new limit for expanding the patient selection criteria. The usefulness of portal pressure measurement to predict the outcome of patients and define optimal candidates for resection has been validated in Japan.12 Thus, resection should remain the first option for patients who have the optimal profile, as defined by the BCLC staging system. Although resection can be performed in some of these patients with advanced liver disease, the mortality is higher and they might be better served by liver transplantation or ablation. A cohort study of radiofrequency ablation demonstrated that complete ablation of lesions smaller than 2 cm is possible in more than 90% of cases, with a local recurrence rate of less than 1%.13 These data should be confirmed by other groups before positioning ablation as the first-line approach for very early HCC. The recommendations regarding patient selection and method of administration of chemoembolization are unchanged. Radioembolization, i.e., the intra-arterial injection of yttrium-90 bound to glass beads or to resin, has been shown to induce tumor necrosis, but there are no data comparing its efficacy to transarterial chemoembolization or to sorafenib treatment for those with portal vein invasion. However, for patients who have either failed transarterial chemoembolization or who present with more advanced HCC, new data indicates the efficacy of sorafenib (a multikinase inhibitor with activity against Raf-1, B-Raf, vascular endothelial growth factor receptor 2, platelet-derived growth factor receptor, c-Kit receptors, among other kinases) in prolonging life.14,15 Sorafenib induces a clinically relevant improvement in time to progression and in survival The magnitude of the improvement in survival compares with other established molecular targeted therapies for other advanced cancers, and the associated toxicity is easily managed without treatment-related mortality. The most frequent adverse events were diarrhea (sorafenib versus placebo: 11% versus 2%) and hand–foot skin reaction (sorafenib versus placebo: 8% versus <1%), fatigue, and weight loss. Sorafenib is now considered first-line treatment in patients with HCC who can no longer be treated with potentially more effective therapies. In summary, in the past decade HCC has gone from being an almost universal death sentence to a cancer that can be prevented, detected at an early stage, and effectively treated. Physicians caring for patients at risk need to provide high-quality screening, proper management of screen-detected lesions, and provision of therapy that is most appropriate for the stage of disease.

                Author and article information

                Hepatol Int
                Hepatol Int
                Hepatology International
                Springer India (New Delhi )
                13 November 2015
                13 November 2015
                January 2016
                : 10
                : 1
                : 1-98
                [ ]Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
                [ ]Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong SAR, China
                [ ]Department of Hepatogastroenterlogy, Sindh Institute of Urology and Transplantation, Karachi, Pakistan
                [ ]Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
                [ ]Genomics Research Center, Academia Sinica, National Taiwan University, Taipei, Taiwan
                [ ]Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
                [ ]Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
                [ ]Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
                [ ]Liver Research Unit, Chang Gung Memorial Hospital and University, Chilung, Taiwan
                [ ]Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
                [ ]New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand
                [ ]Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Guangzhou, China
                [ ]Department of Medicine, Aga Khan University, Karachi, Pakistan
                [ ]Beijing Friendship Hospital, Capital Medical University, Beijing, China
                [ ]Seoul, Korea
                [ ]Department of Medicine, University of Hong Kong, Hong Kong, China
                [ ]Internal Medicine Asan Medical Center, Seoul, Korea
                [ ]Division of Gastroenterology and Hepatology, National University Health System, Singapore, Singapore
                [ ]Research and Molecular Development, Victorian Infectious Diseases Reference Laboratory, Melbourne, Australia
                [ ]Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
                [ ]Department of Medicine, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia
                [ ]Yamanashi Hospitals (Central and Kita) Organization, 1-1-1 Fujimi, Kofu-shi, Yamanashi 400-8506 Japan
                [ ]Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
                [ ]NKC Institute of Gastroenterology and Hepatology, Prince of Songkla University, Songkhla, Thailand
                [ ]Department of Gastroenterology, G.B. Pant Hospital, New Delhi, India
                [ ]Department of Medicine, University of Santo Tomas, Manila, Philippines
                [ ]The Institute of Translational Hepatology, Beijing, China
                [ ]Treatment and Research Center for Infectious Diseases, Beijing 302 Hospital, Beijing, China
                [ ]Peking University Hepatology Institute, Beijing, China
                [ ]Division of Gastroenterology and Hepatology, Department of Medicine, University of Hong Kong, Pofulam, Hong Kong
                [ ]Department of Hepatobiliary and Pancreatic Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003 Zhejiang Province China
                [ ]Graduate Institute of Clinical Medicine and Hepatitis Research Center, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
                © The Author(s) 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                : 20 May 2015
                : 14 September 2015
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                © Asian Pacific Association for the Study of the Liver 2016

                Gastroenterology & Hepatology
                hbv,guidelines,acute hepatitis
                Gastroenterology & Hepatology
                hbv, guidelines, acute hepatitis


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